针对HA-1-向的T细胞受体T细胞治疗在血造干细胞移植后复发性白血病的T细胞治疗
Elizabeth F Krakow1,2, Michelle Brault3, Corinne Summers1,4,5
1Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA.
Blood
|April 29, 2024
概括
针对HA-1抗原 (HA-1 TCR-T) 的工程T细胞显示了干细胞移植后白血病复发的可行性和安全性. 这种治疗证明了初步的疗效,一些患者实现了完全缓解.
科学领域:
- 免疫治疗是一种免疫疗法.
- 造血干细胞移植 造血干细胞移植
- 白血病研究研究 白血病研究
背景情况:
- 针对白血病的复发后异质造血干细胞移植 (HCT) 是死亡的主要原因.
- 经过工程改造以表达T细胞受体 (TCR-T) 的T细胞,向轻微基因相容性 (H) 抗原,为后HCT白血病控制提供了潜在的策略.
- HA-1小H抗原是T细胞介导的抗白血病作用的目标.
研究的目的:
- 评估HA-1 TCR-T细胞在HCT后复发或复发性白血病和髓状瘤患者中使用HA-1 TCR-T细胞的可行性和安全性.
- 评估输液后HA-1 TCR-T细胞的体内扩张和持久性.
- 探索HA-1 TCR-T疗法的初步疗效信号.
主要方法:
- 进行了一项第一阶段临床试验,涉及9名HCT接受者,疾病复发.
- 表达HA-1 TCR和CD8核受体的HA-1 TCR-T细胞是从HA-1-异型HCT供体中制造的.
- 患者在淋巴损伤化疗后接受了一次或多次HA-1 TCR-T输液.
主要成果:
- 从HCT供体中成功制造HA-1 TCR-T细胞.
- 在收养转移后,HA-1 TCR-T细胞在体内扩大并持续存在.
- 没有观察到剂量限制性毒性,这表明了有利的安全性.
- 在9名患者中,有4名患者实现或维持完全缓解,其中1名患者缓解超过两年.
- 单细胞RNA测序揭示了与T细胞功能障碍和复发性白血病中的癌细胞存活相关的上调分子.
结论:
- HA-1 TCR-T疗法是HCT后复发或复发白血病患者的可行和安全的治疗选择.
- 初步的疗效信号表明,HA-1 TCR-T疗法可以诱导和维持缓解.
- 需要进一步研究以优化HA-1 TCR-T疗法及其在HCT环境中的应用.
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